Cysticfibrosis(CF)isageneticdiseasethataffectsthefunctionofavarietyofepithelialorgans,includingthelung,intestine,biliarysystem,andpancreas.Previouslythediseasewasalmostuniformlyfatalduringadolescenceasaresultofsevererespiratoryinfections.However,improvedantibiotics,drugsthatimproveclearanceofmucusfromthelungs,correctionofpancreaticinsufficiencyandundernutrition,andrecentUSFoodandDrugAdministration(FDA)approvalofdrugssuchasivacaftor(Kalydeco)andlumacaftor/ivacaftor(Orkambi)nowextendlifeintothefifthdecadeorlaterinsomepatients.CFiscausedbyamutationinCFTR, whichinthegutimpairstheabilitytohydrateandalkalinizetheluminalcontents.IntheGIsystemspecifically,thiscanresultinintestinalobstruction,duodenalmucosalinjury,anddamagetotheliverandbiliarysystemaswellasthepancreas.InmanyCFpatientstheendocrinepancreasisdysfunctional,andtheymustbegivendigestiveenzymesupplementstomaintainadequatenutrientdigestion.Inotherpatientswithmildermutations,pancreatitismaydeveloplaterinlifeintheabsenceofotherclassicCFsymptoms,presumablybecauseofretentionofdigestiveenzymesinthepancreas.Ineithercase,improvedrecognitionandtreatmentofthepulmonarycomplicationsofCFmeanthatGIsymptomssuchasliverfailure,reducedbileflow,pancreatitis,obstruction,andmaldigestion/malabsorptionofnutrientsareacquiringincreasedimportanceasfacetsofthediseasethatmustbemanagedinadults,oftenbymultidisciplinaryteamsofphysiciansandotherhealthcareprofessionals.
CCK is the product of I cells, which are also localized in the small intestinal epithelium. These classic enteroendocrine cells release CCK into the interstitial space when specific food components are present in the lumen, particularly free fatty acids and certain amino acids. Release of CCK may occur following direct interaction of fatty acids or amino acids, or both, with the I cells. Release of CCK is also regulated by two luminally acting releasing factors that can stimulate the I cell. The first of these, CCK-releasing peptide, is secreted by paracrine cells within the epithelium into the small intestinal lumen in response to products of fat •Fig. 30.5 MechanismsresponsibleforcontrollingreleaseofCCKfromduodenalIcells.ACh,acetylcholine;CCK-RP,CCK-releasingpeptide;GRP,gastrin-releasingpeptide.Solidarrowsrepresentstimulatoryeffects,whereasdashedarrowsindicateinhibition.(RedrawnfromBarrettKE.Gastrointestinal Physiology. NewYork:McGraw-Hill;2006.) and protein digestion. The second releasing factor, monitor peptide, is released by pancreatic acinar cells into pancreatic juice. Both CCK-releasing peptide and monitor peptide can also be released in response to neural input, which is particularly important in initiating pancreatic secretion during the cephalic and gastric phases, thereby preparing the system to digest the meal as soon as it enters the small intestine.
What is the significance of these CCK-releasing factors? Their primary role is to match CCK release, as well as the resulting availability of pancreatic enzymes, to the need for these enzymes to digest the meal in the small intestinal lumen (